# A cell differentiation landscape for monocyte and interstitial macrophage in the lung with diffuse alveolar damage

## TL;DR

This study maps how monocytes and macrophages differentiate in the lungs during a severe lung injury called diffuse alveolar damage, revealing new insights into immune cell behavior and potential treatments.

## Contribution

The study identifies distinct macrophage subsets and a differentiation pathway involving GDF15 in the context of DAD.

## Key findings

- Two distinct macrophage subsets, IMpi and IMai, arise from recruited monocytes in DAD.
- GDF15 promotes the transition from pro-inflammatory to anti-inflammatory macrophages.
- GDF15 deficiency enhances the shift toward pro-inflammatory macrophages.

## Abstract

Diffuse alveolar damage (DAD) is recognized as a deadly type of acute inflammatory lung injury caused by toxic inhalants, but its cellular and molecular pathogenesis remains largely unclear. In this study, by using a mouse model of ricin-induced DAD, we explored the heterogeneity of recruited monocyte (Mono) and Mono-derived interstitial macrophage (IM) in the DAD lung. There was the development of 2 distinct IM subsets, namely IMpi (pro-inflammatory) and IMai (anti-inflammatory), from recruited Monopi. A subset of recruited Monopi could get the proliferating phenotype (namely pMonopi), and meanwhile pMonopi served as the intermediate of Monopi-to-IMai transition. The presence of growth differentiation factor 15 (GDF15) facilitated Monopi-to-pMonopi-to-IMai transition, whereas GDF15 deficiency exerted the negative feedback effect of enhancing Monopi-to-IMpi shift. These findings provided a cell differentiation landscape for Mono and IM in the DAD lung, which would promote a deeper understanding of cellular immunology of DAD and offer a theoretical basis for developing novel therapeutic strategies against acute lung injury.